1. Field of the Invention
This invention relates, generally, to nuclear magnetic resonance (NMR). More specifically, it relates to radiofrequency (RF) transmit-receive coils.
2. Brief Description of the Related Art
Nearly 50% of all the prescription drugs that are in use today were derived from naturally occurring chemicals, also called natural products. In order to identify natural products, they must be fully characterized using spectroscopy techniques such as nuclear magnetic resonance (NMR). NMR is unique in its ability to provide precise information about molecular structure and dynamics. Though NMR is quite powerful, its low sensitivity, however, is a major bottleneck in natural product discovery.
To gain maximum sensitivity, NMR spectrometers are designed to operate at high magnetic field strengths, and consequently the spectrum of NMR signals is in the radio frequency range. The transmit/receive coils are the probe coils that stimulate the nuclei and detect the NMR response from the sample. The sensitivity of the probe coils is primarily dependent on two factors the quality factor (Q-factor) of the coil and the filling factor of the coil. The Q-factor can be improved by constructing the coil out of low loss/resistance materials, such as high temperature superconducting (HTS) materials (Brey, W. W., Edison, A. S., Nast, R. E., Rocca, J. R., Saha, S., and Withers, R. S. (2006) Design, construction, and validation of a 1-mm triple-resonance high-temperature-superconducting probe for NMR, J Magn Reson 179, 290-293; Brey, W. W., Edison, A. S., Hooker, J., Nast, R. E., Ramaswamy, V., and Withers, R. S. (2012) Design, construction and validation of a High-Temperature-Superconducting 13 C optimized 1.5-mm cryogenically cooled NMR probe for natural products and metabolomics, In The 53rd Experimental NMR Conference, Miami, Fla.).
The filling factor can be improved by placing the coil very close to the sample. In multi-channel NMR probes, therefore, the sensitivity of each channel decreases as the distance between coils and the sample increases. Thus, the sensitivity of the probes can be optimized at an inefficient rate of only one channel at a time, namely, the coil placed closest to the sample. Furthermore, another drawback of the probes and methodology of the prior art is that the placement of coils in very close proximity to each other causes undesirable interaction between them.
Another factor affecting sensitivity, aside from materials used (e.g., HTS) and proximity to the sample, is the size of the coil size. Smaller coil sizes tend to lead to more insensitive coils.
An NMR probe coil provides the radiofrequency (RF) magnetic field to the sample, thereby stimulating the nuclear spins, and detects the response of the nuclear spins. When RF current flows through the windings of the NMR probe coil, an RF magnetic field is produced perpendicular to the direction of the current. An RF transmit current forced into the coil produces an RF magnetic field in the sample region, which excites the nuclear spins. Conversely, the RF magnetic field caused by the precession motion of the nuclear spins induces an RF current in the coil windings. In the transmit mode, the strength of the magnetic field decays away with an increase in the distance from the coil, as determined by the Biot-Savart law. By reciprocity, in the receive mode, the strength of the induced current in the coil decays as the distance between sample and coil increases. Under these conditions, it is desirable to design the NMR probe coils to be placed as close as possible to the sample for purposes of optimizing sensitivity.
Another important factor affecting the performance of the RF probe coils is the Q-factor of the coil. The Q-factor can be improved by lowering the resistance and thus the loss in the material of the coil. This may be achieved by either lowering the temperature of the normal metal coils, or by using superconducting material. NMR probe coils are commonly fashioned out of HTS materials. This is achieved by patterning the HTS on planar dielectric substrates. However, such planar coils offer significant constraints to placing the coils very close to the sample.
For NMR excitation and detection of multiple channels, conventional RF probes utilize one (1) pair of coils for each channel. The pair of coils that is placed closest to the sample performs at its optimum to achieve excellent sensitivity. Each additional channel requires a pair of coils nested outside all the other channels. As channels are added, each additional pair of coils must be placed farther away from the sample, providing lower and lower sensitivity. An NMR field frequency lock channel typically used for analytical NMR requires its own coil pair in addition to the others. A typical “triple resonance” NMR probe of the type commonly used for biomolecular structure experiments requires a total of four (4) nested pairs of coils, and of these, only the inner pair is optimized for sensitivity since it is closest to the sample.
The prior art has attempted to improve upon NMR RF probe coils. For example, U.S. Pat. No. 4,973,908 relates to a surface coil for NMR spectroscopy of humans which utilizes a circular coil and a figure-8 or butterfly coil that is produces a magnetic field substantially perpendicular to the circular coil. The '908 patent applies to a surface coil rather than a volume coil, applies to human rather than analytical NMR spectroscopy, is fabricated from freestanding metal rather than deposited on a dielectric substrate, and relies on discrete rather than distributed and integrated capacitive elements to tune to the NMR frequency.
U.S. Pat. No. 4,816,765 describes a surface coil for MRI of human which utilizes coplanar coils of different shapes to generate orthogonal magnetic fields. The coils are intended for quadrature MRI applications.
U.S. Pat. No. 5,565,778 discloses a self-resonant structure known as a “racetrack” which incorporates interdigital capacitors into the NMR coil.
U.S. Pat. No. 5,594,342 describes dividing the current carrying elements into thin strips to avoid distortion of the NMR polarizing field.
U.S. Pat. No. 6,201,392 describes to a number of configurations of parallel superconductive coils to minimize interaction between coils. Simple rectangular coils are partly overlapped or otherwise disposed to null their mutual inductance. A parallel LC trap can be incorporated into the rectangular coil to reduce interaction with other coils at a single frequency. However, this prior art does not teach orthogonal magnetic fields as a means to null the mutual inductance between the coils. Rather, it teaches parallel magnetic fields over the sample region. Parallel magnetic fields have several drawbacks, however. For example, coil independence can be achieved only by requiring adjustment of overlap of coils on a single substrate and/or adjustment of the spacing of coils on independent substrates. Further, the '392 patent does not teach the use of fixed coupling loops which utilize variable capacitors to adjust tuning and matching.
U.S. Pat. No. 7,397,246 relates to methods for combining superconductive and low-Q coils such that the low-Q coils do not spoil the Q of the superconductive coils. The methods involve crossovers in the low-Q coils to reduce capacitive coupling to the superconductive coils.
U.S. Pat. No. 7,446,534 discloses a method to suppress the electric field of the NMR coil fringing into the sample.
U.S. Pat. No. 8,089,281 relates to doubly resonant surface coils with the magnetic fields substantially orthogonal to each other.
However, the foregoing prior art suffers from the one or more of the following disadvantages, despite the increased sensitivity seen in probes formed of HTS materials. Conventional probe coils have been unable to replace the industry standard 5-mm triple resonance probe used in laboratories. Probes that are newly developed tend to be niche probes that are capable of use in very specific applications. Additionally, there are moving elements with HTS probes that are not used in probes based on metal wires. These moveable wire loops adversely affect static magnetic field homogeneity, which makes initial adjustment difficult and reduces the resolution that can be obtained. The loops also can fail and are difficult to repair. Further, patterning multiple coils close to each other causes interference that can affect the reproducibility of results.
In a conventional NMR probe, metal wire or foil loops surrounding the sample convert a tiny RF magnetic field from the sample into electrical signals which are detected by the spectrometer. The conversion is not an efficient process because of the resistance of the metal. In an HTS probe, self-resonant coils are formed of thin-film oxide superconductors, such as yttrium barium copper oxide (YBCO), instead of metal. This is used as NMR detection coils because of their extremely high quality factors and nearly loss-free qualities in the NMR frequency range. The film is available as a coating on polished sapphire wafers. Electrical energy is coupled into and out of these coils by means of inductive coupling to a wire loop at the end of a coaxial transmission line. Mechanical adjustment of the position of the wire loop is used to adjust the coupling to match the coil impedance to the characteristic impedance of the transmission line. A related adjustment of radio frequency properties is known as tuning. Tuning refers to a shift in resonant frequency of the NMR coil. In HTS, this shift is accomplished by moving a shorted wire loop so that it intercepts a variable amount of flux from the NMR coil.
The moving loop approach for tuning and matching has some important disadvantages. Most importantly, moving a loop and coaxial cable close to the NMR sample tends to change the uniformity of the polarizing magnetic field. In NMR, chemical resolution is typically limited by the uniformity of the polarizing field. Great effort is made to adjust this uniformity in a process called “shimming.” Even if the loop is made from high quality susceptibility-compensated wire, the effect is noticeable. It is, therefore, not possible to adjust the RF coupling (known as matching) or the tuning without affecting the resolution, requiring a time-consuming step of re-shimming the magnet.
Another drawback of moving loops is basic to the use of moving parts in almost any device. Moving parts tend to be less reliable than other approaches, as there is higher chance of inefficiencies and failure.
Additionally, the number of nested pairs required for a triple resonance NMR probe places a limit on the sample diameter that can practically be accommodated. To achieve reasonable sensitivity and field homogeneity, each coil pair must be at least as wide as the gap between the coils. Within a “standard bore” NMR magnet, shim and pulsed field gradient coil, there is not enough room to nest more than about three (3) channels around a standard 5-mm diameter sample tube. There is very little space available in NMR probes, and the need for independent loops for the two functions makes the design, construction, adjustment and repair of HTS NMR probes significantly more difficult and time consuming. There is insufficient space to accommodate the coils required for a triple resonance probe that requires four (4) channels and four (4) nested pairs.
Accordingly, what is needed is an NMR probe that has multiple RF coils in close proximity with each other and with the sample, while producing a strong and homogenous magnetic field at both frequencies that reduces electric fields within the sample region and while also minimizing the interaction between the RF coils. With HTS materials, fewer superconducting materials should be needed, thus allowing for a larger, standard-sized sample, while eliminating moving parts, in turn improving reliability and reproducibility of results. However, in view of the art considered as a whole at the time the present invention was made, it was not obvious to those of ordinary skill in the field of this invention how the shortcomings of the prior art could be overcome.
All referenced publications are incorporated herein by reference in their entirety. Furthermore, where a definition or use of a term in a reference, which is incorporated by reference herein, is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies and the definition of that term in the reference does not apply.
While certain aspects of conventional technologies have been discussed to facilitate disclosure of the invention, applicants in no way disclaim these technical aspects, and it is contemplated that the claimed invention may encompass one or more of the conventional technical aspects discussed herein.
The present invention may address one or more of the problems and deficiencies of the prior art discussed above. However, it is contemplated that the invention may prove useful in addressing other problems and deficiencies in a number of technical areas. Therefore, the claimed invention should not necessarily be construed as limited to addressing any of the particular problems or deficiencies discussed herein.
In this specification, where a document, act or item of knowledge is referred to or discussed, this reference or discussion is not an admission that the document, act or item of knowledge or any combination thereof was at the priority date, publicly available, known to the public, part of common general knowledge, or otherwise constitutes prior art under the applicable statutory provisions; or is known to be relevant to an attempt to solve any problem with which this specification is concerned.